Cerebral dopamine neurotrophic factor protects H9c2 cardiomyocytes from apoptosis

Cerebral dopamine neurotrophic factor (CDNF) has been studied in animal models of Parkinson's disease, where it was shown to repair and protect dopamine neurons. Alongside its neurotrophic activity, it can also localize in the endoplasmic reticulum (ER) acting as an ER stress response (ERSR) protein to maintain ER homeostasis. Since ER stress plays a major role in the development and progression of cardiovascular diseases, we investigated the role of CDNF in cardiomyocytes during ER stress. Initially, the expression of CDNF was tested by treating H9c2 cells with various concentrations of tunicamycin (TM) and performing reverse-transcriptase polymerase chain reaction and Western blotting. To evaluate the overexpression of CDNF in cardiomyocytes, H9c2 cells were transfected with pcDNA-CDNF and analyzed by Western blotting and indirect immunofluorescence microscopy. The effects of CDNF on cardiomyocytes during ER stress were analyzed with CCK-8 method and TUNEL staining using cells transfected with pcDNA-CDNF or pcDNA3.1. The percentage of TUNEL-positive cells was quantified as the apoptotic level. Our results showed that CDNF protein expression can be induced by activation of ER stress in cultured cardiomyocytes. Moreover, overexpression of CDNF improved cell viability and protected cardiomyocytes from apoptosis induced by ER stress. The findings presented here contribute toward identifying the physiological functions of CDNF in cardiovascular diseases.